Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2UXWH9)

• DOT Name: Optineurin (OPTN)
• Synonyms: E3-14.7K-interacting protein; FIP-2; Huntingtin yeast partner L; Huntingtin-interacting protein 7; HIP-7; Huntingtin-interacting protein L; NEMO-related protein; Optic neuropathy-inducing protein; Transcription factor IIIA-interacting protein; TFIIIA-IntP
• Gene Name: OPTN
• Related Disease:
  Amyotrophic lateral sclerosis type 12
  Glaucoma, normal tension, susceptibility to
  Neoplasm
  Advanced cancer
  Alzheimer disease
  Amyloidosis
  Amyotrophic lateral sclerosis type 1
  Amyotrophic lateral sclerosis-parkinsonism-dementia complex
  Astrocytoma
  Bone disease
  Brain neoplasm
  Carcinoma
  Coeliac disease
  Colitis
  Disorder of orbital region
  Familial amyotrophic lateral sclerosis
  Frontotemporal dementia
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Huntington disease
  Idiopathic thrombocytopenic purpura
  Immunodeficiency
  Inflammatory bowel disease
  Motor neurone disease
  Myopathy
  Obsolete glaucoma 1, open angle, E
  Pick disease
  Prostate cancer
  Tuberculosis
  Breast cancer
  Breast carcinoma
  Clear cell renal carcinoma
  Diabetic kidney disease
  Parkinson disease
  Renal cell carcinoma
  Amyotrophic lateral sclerosis
  Adult glioblastoma
  Blindness
  Chronic renal failure
  Crohn disease
  End-stage renal disease
  Glioblastoma multiforme
  Glioma
  IgA nephropathy
  Neuroblastoma
  Paget's disease
  Prostate carcinoma
• UniProt ID: OPTN_HUMAN
• PDB ID: 2LO4; 2LUE; 3VTV; 3VTW; 5AAZ; 5B83; 5EOA; 5EOF; 7CZM
• Pfam ID: PF16516 ; PF11577 ; PF18414
• Sequence:
  MSHQPLSCLTEKEDSPSESTGNGPPHLAHPNLDTFTPEELLQQMKELLTENHQLKEAMKL
  NNQAMKGRFEELSAWTEKQKEERQFFEIQSKEAKERLMALSHENEKLKEELGKLKGKSER
  SSEDPTDDSRLPRAEAEQEKDQLRTQVVRLQAEKADLLGIVSELQLKLNSSGSSEDSFVE
  IRMAEGEAEGSVKEIKHSPGPTRTVSTGTALSKYRSRSADGAKNYFEHEELTVSQLLLCL
  REGNQKVERLEVALKEAKERVSDFEKKTSNRSEIETQTEGSTEKENDEEKGPETVGSEVE
  ALNLQVTSLFKELQEAHTKLSEAELMKKRLQEKCQALERKNSAIPSELNEKQELVYTNKK
  LELQVESMLSEIKMEQAKTEDEKSKLTVLQMTHNKLLQEHNNALKTIEELTRKESEKVDR
  AVLKELSEKLELAEKALASKQLQMDEMKQTIAKQEEDLETMTILRAQMEVYCSDFHAERA
  AREKIHEEKEQLALQLAVLLKENDAFEDGGRQSLMEMQSRHGARTSDSDQQAYLVQRGAE
  DRDWRQQRNIPIHSCPKCGEVLPDIDTLQIHVMDCII
• Function: Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8. Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation. Plays a role in the activation of innate immune response during viral infection. Mechanistically, recruits TBK1 at the Golgi apparatus, promoting its trans-phosphorylation after RLR or TLR3 stimulation. In turn, activated TBK1 phosphorylates its downstream partner IRF3 to produce IFN-beta/IFNB1. Plays a neuroprotective role in the eye and optic nerve. May act by regulating membrane trafficking and cellular morphogenesis via a complex that contains Rab8 and hungtingtin (HD). Mediates the interaction of Rab8 with the probable GTPase-activating protein TBC1D17 during Rab8-mediated endocytic trafficking, such as that of transferrin receptor (TFRC/TfR); regulates Rab8 recruitment to tubules emanating from the endocytic recycling compartment. Autophagy receptor that interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family; targets ubiquitin-coated bacteria (xenophagy), such as cytoplasmic Salmonella enterica, and appears to function in the same pathway as SQSTM1 and CALCOCO2/NDP52; (Microbial infection) May constitute a cellular target for various viruses, such as adenovirus E3 14.7 or Bluetongue virus, to inhibit innate immune response. During RNA virus infection, such as that of Sendai virus, negatively regulates the induction of IFNB1.
• Tissue Specificity: Present in aqueous humor of the eye (at protein level). Expressed in the trabecular meshwork (at protein level) . Expressed in nonpigmented ciliary epithelium (at protein level) . Expressed at high levels in skeletal muscle, also detected in heart, brain, pancreas, kidney, placenta and liver . Expressed in dermal fibroblasts (at protein level) .
• KEGG Pathway:
  Mitophagy - animal (hsa04137)
  Autophagy - animal (hsa04140)
  Amyotrophic lateral sclerosis (hsa05014)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway:
  TNFR1-induced proapoptotic signaling (R-HSA-5357786)
  Regulation of TNFR1 signaling (R-HSA-5357905)
  TNFR1-induced NF-kappa-B signaling pathway (R-HSA-5357956)
  TBC/RABGAPs (R-HSA-8854214)
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis type 12	DISLNZU8	Definitive	Semidominant	[1]
Glaucoma, normal tension, susceptibility to	DISRAZKV	Definitive	Autosomal dominant	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Amyloidosis	DISHTAI2	Strong	Biomarker	[5]
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Strong	Genetic Variation	[6]
Amyotrophic lateral sclerosis-parkinsonism-dementia complex	DISTHQI1	Strong	Biomarker	[7]
Astrocytoma	DISL3V18	Strong	Altered Expression	[8]
Bone disease	DISE1F82	Strong	Genetic Variation	[9]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[10]
Carcinoma	DISH9F1N	Strong	Biomarker	[11]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[12]
Colitis	DISAF7DD	Strong	Biomarker	[13]
Disorder of orbital region	DISH0ECJ	Strong	Genetic Variation	[14]
Familial amyotrophic lateral sclerosis	DISWZ9CJ	Strong	Biomarker	[15]
Frontotemporal dementia	DISKYHXL	Strong	Biomarker	[16]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[17]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[18]
Huntington disease	DISQPLA4	Strong	Biomarker	[19]
Idiopathic thrombocytopenic purpura	DISFKGJU	Strong	Altered Expression	[20]
Immunodeficiency	DIS093I0	Strong	Biomarker	[21]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[22]
Motor neurone disease	DISUHWUI	Strong	Genetic Variation	[23]
Myopathy	DISOWG27	Strong	Biomarker	[24]
Obsolete glaucoma 1, open angle, E	DISL7Q3J	Strong	Autosomal dominant	[25]
Pick disease	DISP6X50	Strong	Biomarker	[16]
Prostate cancer	DISF190Y	Strong	Biomarker	[26]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[27]
Breast cancer	DIS7DPX1	moderate	Biomarker	[28]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[28]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[29]
Diabetic kidney disease	DISJMWEY	moderate	Altered Expression	[30]
Parkinson disease	DISQVHKL	moderate	Biomarker	[31]
Renal cell carcinoma	DISQZ2X8	moderate	Biomarker	[29]
Amyotrophic lateral sclerosis	DISF7HVM	Supportive	Autosomal dominant	[32]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[33]
Blindness	DISTIM10	Limited	Genetic Variation	[14]
Chronic renal failure	DISGG7K6	Limited	Genetic Variation	[34]
Crohn disease	DIS2C5Q8	Limited	Biomarker	[22]
End-stage renal disease	DISXA7GG	Limited	Genetic Variation	[34]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[33]
Glioma	DIS5RPEH	Limited	Altered Expression	[35]
IgA nephropathy	DISZ8MTK	Limited	Genetic Variation	[34]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[36]
Paget's disease	DISO3MC0	Limited	Genetic Variation	[37]
Prostate carcinoma	DISMJPLE	Limited	Genetic Variation	[38]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Optineurin (OPTN) affects the response to substance of Topotecan.	[65]

25 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Optineurin (OPTN).	[39]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Optineurin (OPTN).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Optineurin (OPTN).	[41]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Optineurin (OPTN).	[42]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Optineurin (OPTN).	[43]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Optineurin (OPTN).	[44]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Optineurin (OPTN).	[45]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Optineurin (OPTN).	[46]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Optineurin (OPTN).	[49]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Optineurin (OPTN).	[50]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Optineurin (OPTN).	[50]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Optineurin (OPTN).	[51]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Optineurin (OPTN).	[44]
Selenium	DM25CGV	Approved	Selenium increases the expression of Optineurin (OPTN).	[52]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Optineurin (OPTN).	[53]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Optineurin (OPTN).	[54]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Optineurin (OPTN).	[55]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Optineurin (OPTN).	[56]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Optineurin (OPTN).	[57]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Optineurin (OPTN).	[59]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Optineurin (OPTN).	[60]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Optineurin (OPTN).	[61]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Optineurin (OPTN).	[62]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Optineurin (OPTN).	[63]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Optineurin (OPTN).	[64]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Optineurin (OPTN).	[47]
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Optineurin (OPTN).	[48]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Optineurin (OPTN).	[58]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Optineurin (OPTN).	[48]

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